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GDC-4198 alone and with giredestrant versus abemaciclib plus giredestrant for advanced ER+, HER2- breast cancer

A Phase Ib/II Multicenter, Open-Label, Randomized Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 Alone and in Combination With Giredestrant in Comparison With Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer Who Have Previously Progressed During or After a CDK4/6 Inhibitor

Phase1; Phase2 Interventional Genentech, Inc. · NCT07100106

This study will test whether the new drug GDC-4198, alone or with giredestrant, works better or is as safe as abemaciclib plus giredestrant for people with advanced or metastatic ER-positive, HER2-negative breast cancer who progressed after CDK4/6 inhibitors.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment285 (estimated)
Ages18 Years and up
SexAll
SponsorGenentech, Inc. Industry-sponsored
Drugs / interventionschemotherapy
Locations35 sites (Duarte, California and 34 other locations)
Trial IDNCT07100106 on ClinicalTrials.gov

What this trial studies

The trial has two parts: a Phase Ib dose-finding and safety stage to characterize the tolerability and pharmacokinetics of GDC-4198 alone and in combination with the oral selective estrogen receptor degrader giredestrant, followed by a randomized Phase II comparison of GDC-4198 plus giredestrant versus abemaciclib plus giredestrant. Phase Ib will enroll participants to define safe doses and monitor adverse events and PK parameters, while Phase II will compare activity and safety between the combination arms using standard response and progression endpoints. Eligible participants have locally advanced or metastatic ER+, HER2- breast cancer and prior progression on a CDK4/6 inhibitor and endocrine therapy. Treatment is given systemically and patients are followed for tumor response, safety, and survival outcomes.

Who should consider this trial

Good fit: Adults with histologically confirmed locally advanced or metastatic ER-positive, HER2-negative breast cancer who progressed during or after approved CDK4/6 inhibitor therapy and endocrine therapy, with ECOG 0–1 and life expectancy of at least 6 months, are the intended candidates.

Not a fit: Patients with rapidly progressing, symptomatic visceral disease at high short-term risk of life-threatening complications or those who do not meet prior-CDK4/6 inhibitor exposure criteria are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the combination with GDC-4198 could offer an effective new treatment option for patients whose ER+ HER2- breast cancer progressed after CDK4/6 inhibitors.

How similar studies have performed: CDK4/6 inhibitors combined with endocrine therapy have proven benefit in this setting and newer oral SERDs like giredestrant have shown promise, but GDC-4198 itself is a novel agent being tested in early-phase trials.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic.
* Previously documented ER+ and HER2- tumor according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines.
* Disease progression during or after treatment with an approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and approved endocrine therapy (ET) in the locally advanced or metastatic setting.
* Measurable or non-measurable evaluable, disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Life expectancy \>= 6 months.

Exclusion Criteria:

* Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines.
* Have received more than one-line of therapy for locally advanced or metastatic disease.
* Have received prior chemotherapy for metastatic breast cancer.
* Treatment with an approved oral ET within 7 days prior to initiation of study drug; treatment with fulvestrant or an approved CDK4/6 inhibitor within 21 days prior to initiation of study drug.
* Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption
* History of malignancy within 3 years prior to screening, except for cancer under investigation in this study and malignancies with a negligible risk of metastasis or death.
* Known allergy or hypersensitivity to any component of the study treatments.

Where this trial is running

Duarte, California and 34 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Breast Cancer
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.